Danielle Grée

The Small Organic Compound HA14-1 Prevents Bcl-2 Interaction with Bax to Sensitize Malignant Glioma Cells to Induction of Cell Death

A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is likely to participate in the resistance of cancer cells to therapy. We show here that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to function as an inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to radiotherapy and chemotherapy. This sensitizing effect is lost if Bcl-2 expression, but not Bcl-xL expression, is knocked down or if cells only express a mutant of Bax that does not interact with Bcl-2. This points to a specific Bcl-2 inhibitory function of HA14-1 and implies that it selectively involves hindrance of Bcl-2 binding to Bax, which HA14-1 inhibits in cell-free assays and in cells in receipt of an apoptotic stimulation. Moreover, HA14-1, in combination with a cytotoxic treatment, slows down the growth of glioblastoma in vivo. Thus, the inhibition of Bcl-2 achieved by HA14-1 might improve treatment outcome.

Flexible Synthesis of Pyrimidines with Chiral Monofluorinated and Difluoromethyl Side Chains

Chiral pyrimidines with a fluorine atom in the benzylic position are easily accessible in high enantiomeric excesses from optically active propargylic intermediates by two complementary routes. Both the use of optically active propargylic fluorides and the fluorination of the chiral pyrimidine in the final stage give excellent results in terms of enantiocontrol. On the other hand, original pyrimidines with a difluoromethyl side chain are also obtained in a few steps from new propargylic ketones bearing a CHF(2) substituent on the triple bond.

The use of circular dichroism for the determination of the absolute configuration of chiral butadiene-tricarbonyl iron complexes

Abstract The circular dichroism spectra of functionalized butadiene-tricarbonyliron complexes can be used to predict the absolute configuration of these organometallic derivatives.

Substituent effects on the regioselectivity in fluorination of allylic alcohols with DAST

Abstract The regioselectivity of the fluorination of various allylic and β-dienoic alcohols with DAST has been studied. Substituent effects are important in these reactions; a strong preference for the secondary fluorides versus the primary ones is observed, especially in the case of alkyl and aryl substituted derivatives.

High regio-and stereocontrol in the dehydroxy — fluorination of propargylic alcohols and the corresponding Cobalt-carbonyl complexes

Abstract The reaction of DAST with chiral propargylic alcohols 1 and 2 occurs with high stereoselectivities and in a stereodivergent manner; this is the first example for the use of Cobalt-carbonyl complexes in nucleophilic fluorination.

Synthesis and reactivity of E,Z butadiene-iron tricarbonyl complexes

Abstract The synthesis, structure and thermal stability of the E,Z butadiene-iron tricarbonyl complex 1 is reported. This complex reacts with organometallic nucleophiles in a stereoselective synthesis of functionalized E,Z dienes.

A new metal mediated stereocontrolled synthesis of allylic fluorides

Abstract Propargylic fluorides are converted in a short sequence involving hydrostannylation, iodination and Pd catalysis into new stereodefined polyunsaturated systems with a fluorine atom in the allylic position.

A new stereoselective synthesis of chiral optically pure 4-piperidones

Abstract A novel approach to optically pure and functionalized 4-piperidones using diene tricarbonyl iron complexes is described.

A NEW HIGHLY STEREOSELECTIVE MONOFLUORINATION IN BENZYLIC POSITION

Abstract Reaction of DAST with secondary alcohols vicinal to an arene Cr(CO) 3 unit gives with very high exo stereoselectivity the corresponding fluorides; the stereochemistry of the reaction appears to be exclusively controlled by the organometallic moiety.

Highly enantioselective propargylic monofluorination established by carbon-13 and fluorine-19 NMR in chiral liquid crystals

Carbon-13 and fluorine-19 NMR experiments in a chiral polypeptide liquid crystalline solvent (PBLG) are used to establish enantioselective propargylic monofluorination.